Flash Synthesis of Spherical Nucleic Acids with Record DNA Density

Nanoparticles (NPs) decorated with a high density of DNA strands, also known as spherical nucleic acids (SNAs), are widely used in DNA-programmable assembly, sensing, imaging, and therapeutics. A regular SNA synthesis is very time-consuming, which requires great caution to avoid NP aggregation. Herein we report an extremely simple, efficient, and scalable process to realize instant (in seconds) synthesis of SNAs with record-high DNA density. Our method relies on a rapid water removal from a DNA/NP mixture in contact with a butanol phase. This process generates a dehydrated "solid solution" that greatly accelerates DNA anchorage on NPs via Au-S bonding. Compared to a state-of-the-art DNA conjugation strategy in the literature, up to 3-time increase of DNA density is achieved by the instant dehydration in butanol (INDEBT). The ultradense DNA grafting is accomplished in a few seconds, which is highly hybridizable to form core-satellite assemblies. Our work turns SNA synthesis into an easy job, and enables future explorations of physical, chemical, and biological effects of SNAs with ultrahigh DNA density.